smoking cessation facilitated by glucagon-like peptide-1 (glp-1) analogues

Conditions: Glucagon-like Peptide-1; Smoking Cessation; Weight Change, Body; Craving

Summary: cigarette smoking is the leading preventable cause of premature death worldwide. however smoking is a very difficult addiction to break whereby main reasons for not quitting or relapsing after cessation are the nicotine withdrawal syndrome and post-cessational weight gain. glp-1 analogues are well known to stimulate insulin secretion and to reduce energy intake and therefore body weight. recent findings from animal and human studies suggest a role of glp-1 in the pathophysiology of addiction. the putative role of glp-1 analogues in nicotine reward regulation combined with its weight reducing effects might be of major interest in view of novel pharmacotherapeutic options for smoking cessation. * substudy "fmri": this substudy is to evaluate effects of dulaglutide treatment on functional neuronal changes in smokers who want to quit smoking. * substudy "energy": this substudy is to investigate the effect of dulaglutide (trulicity®) on ree and further parameters associated with energy metabolism (bodycomposition, haemodynamic parameters and catecholamine action) in a subset of patients recruited for the main trial.

cigarette smoking is the leading preventable cause of premature death worldwide. however smoking is a very difficult addiction to break and despite established smoking cessation programs quit rates are low, especially in the real-life setting. the main reasons for not quitting or relapsing after cessation are the nicotine withdrawal syndrome and post-cessational weight gain. glp-1 analogues are well known to stimulate insulin secretion and to reduce energy intake and therefore body weight. recent findings from animal and human studies suggest a role of glp-1 in the pathophysiology of addiction. the putative role of glp-1 analogues in nicotine reward regulation combined with its weight reducing effects might be of major interest in view of novel pharmacotherapeutic options for smoking cessation. * substudy "fmri" (60 patients): supposing that glp-1 and analogues modulates nicotine induces reward system this substudy is to analyze if treatment with dulaglutide (trulicity®) attenuates craving and therefore functional brain activation. it is to evaluate effects of dulaglutide treatment on functional neuronal changes in smokers who want to quit smoking. * substudy "energy" (60 patients): the aim of the substudy "energy" is to investigate the effect of dulaglutide (trulicity®) on ree and further parameters associated with energy metabolism (bodycomposition, haemodynamic parameters and catecholamine action) in a subset of patients recruited for the main trial.

Eligibility criteria:
inclusion criteria for the main study: * age 18 to 75 years * daily smokers who are willing to quit and exhibit one of the following criteria: ≥10 cigarettes per day or * at least moderate nicotine dependence defined by a fagerstroem score of ≥5 points or * tobacco associated disease * treatment with varenicline (champix®) additional inclusion criteria for the "substudy fmri": * only patients aged 18-50 years are eligible additional inclusion criteria for the "substudy energy": * bmi of 18-30 kg/m2 exclusion criteria for the main study: * pregnancy (incl. wish to become pregnant within next 3 months) or breast feeding * pre-existing treatment with glp-1 agonists * history of pancreatitis * severe renal insufficiency (estimated glomerular filtration rate smaller than 30 ml/min/1.73 m2) * instable psychiatric conditions * anorexia nervosa additional exclusion criteria for the "substudy fmri": * medical conditions that affect brain function (e.g. stroke, epilepsy, space occupying lesions, multiple sclerosis, parkinson's disease, dementia, transient ischemic attack), * current use of medications that alter brain function * current illicit drug abuse including marijuana (alcohol ≤ 1 drink per day allowed) * claustrophobia, cardiac pacemaker, electronic device or ferromagnetic metal foreign bodies